1. Field of the Invention
The present invention is directed to a dental health composition and method for reducing the onset of dental caries and plaque-associated periodontal disease. More particularly, the invention involves a group of modified dextrans which reduce dental plaque formation by reducing and/or modifying the activity of plaque-producing glucosyltransferase (GTF) enzymes secreted by bacteria in the mouth.
2. Description of the Prior Art
The term "GTF" is used to abbreviate a group of extracellular glucosyltransferase enzymes elaborated by numerous strains of cariogenic Streptococcus Mutans bacteria which are known to inhabit the oral environment, multiplying on the teeth and gums. The bacteria-produced enzymes rapidly convert ingested sucrose into large polymers of glucose, called glucans or dextrans, which adhere to tooth enamel and other oral surfaces including dental appliances.
As is well-known in the art, the gradual accumulation of glucans on oral surfaces results in a film of sticky dental plaque if left untreated. Plaque causes dental caries and related periodontal disorders because it provides a protective matrix within which cariogenic S. Mutans bacteria will readily colonize. Plaque also causes agglomeration of food debris on dental surfaces and prevents salivary neutralization of harmful lactic acid secreted by bacterial cells lodged in the plaque matrix. Despite efforts to counteract plaque with ordinary hygiene measures such as brushing and flossing, plaque deposition in many instances will still result in the gradual appearance of carious lesions in the teeth. Such lesions occur when tooth enamel is dissolved by lactic acid secreted into the plaque matrix as a by-product of metabolic processes on-going in plaque-bound bacterial cells.
Glucan molecules, the principal component of dental plaque, are enormous soluble and insoluble polymers of glucose having molecular weights as high as 10.sup.6. By a mechanism postulated in Robyt, et al., Arch. Biochem. Biophys., Volume 165, p. 634 (1974), glucose units obtained from dietary sucrose are converted by GTF enzymes into polymers of glucose called dextrans, many of which, after sufficient lenghtening and branching, exhibit properties of insolubility and adhesiveness characteristic of high molecular-weight plaque glucans. Although the GTF-mediated synthesis of glucans can begin with a single glucose unit, the rate of polymer enlargement will increase only gradually and then level off when the molecule has reached a molecular weight of approximately 6,000. However, this slow initial growth phase can be accelerated if, instead of single glucose units, low molecular-weight dextrans are provided as the starting material for the GTF reaction. These smaller glucose polymers are commonly referred to as dextran primers.
The mechanism of GTF-catalyzed glucan synthesis and the phenomenon that dextrans act as primers for GTF synthesis of plaque glucans have led to investigation whether certain chemically modified dextrans might exhibit an opposite effect upon the GTF reaction, namely, a reduction of glucan synthesis by attachment to the GTF enzyme binding site to form an enzyme/modified primer complex which appreciably slows down further glucan synthesis. The expected utility of such hypothetical blocking compounds can be readily appreciated when contrasted with present anti-caries, anti-plaque hygienic measures such as tooth-brushing and fluoride rinses which attempt with only marginal success to eradicate existing plaque and bacterial build-up.
Robyt et al., U.S. Pat. No. 4,228,150 disclosed that fluorosucroses substituted with fluorine for at least the C.sub.6 hydroxyl group of sucrose (and possibly other hydroxyls) inhibited GTF synthesis of dextran from sucrose. Robyt et al., U.S. Pat. No. 4,335,100 further disclosed a method for inhibiting GTF enzyme involving use of substituted sucrose compounds having an inhibiting group bonded to the 5'-position ring carbon. The inhibiting group was one of the following groups: --CH.sub.2 X, .dbd.CH.sub.2, --CHO, or H (wherein X is selected from the class consisting of --Cl, --Br, I, --N.sub.3, --NH.sub.2, --OCH.sub.3, or --H).
Thaniyavarn, S. et al, "Kinetic Analysis for the Inhibition of Dextransucrase by Aminosugars" in Proceedings `Glucosyltransferases, Glucans, Sucrose and Dental Caries` Editors: Doyle, R. J. and Ciardi, J. E. Sp. Supp. Chemical Senses, 1983; pp. 161-170 (1983), disclosed that the sugars 6,6'-diamino-6,6'-dideoxysucrose, 6'-amino-6'deoxysucrose, 6-amino-6-deoxysucrose, and 6-amino-6-deoxymethyl-a-D-glucopyranoside, are inhibitors of the enzyme dextransucrase.
Miyasaki, T. and Newbrun, E. "Inhibition of Adherence of Streptococcus mutans by Acarbose", in Proceedings `Glucosyltransferases, Glucans, Sucrose and Dental Caries` Editors: Doyle, R. J. and Ciardi, J. E. Sp. Supp. Chemical Senses, 1983; pp. 201-210 (1983), disclosed that the pseudotetrasaccharide consisting of the seven-carbon cyclitol unit linked to the amino group of 4-amino-4,6-dideoxyglucose which, in turn, is in alpha 1,4 linkage to a maltose disaccharide, inhibits synthesis of water-insoluble glucans by glucosyltransferase enzyme.
Other research to identify GTF inhibitors involved modification of dextran through partial periodate oxidation.
See Inoue et al., Carbohydrate Research, Volume 80, pp. 163-177 (1980). Inoue et al. disclosed that commercially available branched dextran, when modified by an oxidative scission of covalent bonds between carbon atoms 2 and 3 in an undetermined percentage of glucose units in the dextran, exhibited potent in-vitro GTF-deactivation. GTF inhibition by the oxidized dextran was postulated to result from an interaction between 2,3-dialdehyde groups present in the partially oxidized dextran and reactive functional groups close to the dextran binding site of the GTF enzyme.
The most recently disclosed GTF inhibitor known by applicant is the compound homocitric acid oligoriboside as claimed in Okami et al., U.S. Pat. No. 4,376,761.